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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,351 records · Page 75Linked to original sources
PubMed1994

Application of angiogenic oligosaccharides of hyaluronan increases blood vessel numbers in rat skin.

Angiogenic oligosaccharides of hyaluronan were applied to the backs of young, adult male rats and the number of blood vessels, within a depth of 136 microns beneath the base of the epidermis, were evaluated. Application of hyaluronan oligosaccharides significantly increased the mean number of blood vessels/mm skin length in six of 11 treated rats when compared with controls. Application of radiolabeled hyaluronan oligosaccharides to skin of one rat demonstrated a penetration to a depth of approximately 800 microns, suggesting that the blood vessels beneath the epidermis would be exposed to the hyaluronan. Hyaluronan has previously been shown to stimulate endothelial cell proliferation; we demonstrate here that these hyaluronan oligosaccharides also specifically stimulate endothelial cell migration. This action of hyaluronan oligosaccharides may prove useful in retarding blood vessel paucity and degeneration observed during the ageing process and following radiotherapy.

Animals↗
PubMed1994

Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism.

OBJECTIVE: A high prevalence of diabetes mellitus has been shown in patients with primary hyperparathyroidism (PHPT). However, it is unclear whether this is related to the metabolic abnormalities in PHPT or to the presence of other risk factors for glucose intolerance in these patients. The aim of our study was to determine whether glucose intolerance and insulin insensitivity occur in subjects with PHPT who do not have other risk factors for diabetes mellitus. DESIGN: Cross-sectional study of glucose metabolism in PHPT patients without other risk factors for diabetes mellitus, compared to age and body mass index (BMI) matched healthy subjects. SUBJECTS: Nineteen non-obese, non-diabetic, normotensive patients with PHPT and 11 age and BMI matched healthy subjects. MEASUREMENTS: The continuous infusion of glucose test was used to assess glucose tolerance. Plasma glucose and insulin were measured during a 1-hour continuous infusion of glucose (5 mg/kg ideal body weight/min); insulin sensitivity and beta-cell function were derived from the glucose and insulin data by mathematical modelling. Fasting serum concentrations of parathyroid hormone, ionized calcium and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in all subjects. RESULTS: PHPT patients attained higher plasma glucose levels at the end of the glucose infusion (median 9.0 (interquartile range 8.1-9.8) mmol/l) than did controls (7.9 (7.1-8.9) mmol/l, P < 0.05), and 8 (42%) PHPT patients had impaired glucose tolerance. Insulin sensitivity was lower in PHPT (60.3% (49.8-85.4)) than in controls (113.7% (89.3-149.2), P < 0.001); beta-cell function was not different in PHPT subjects. PHPT subjects with impaired glucose tolerance had reduced beta-cell function compared to PHPT subjects with normal glucose tolerance (89.9% (70.5-106.4) vs 120% (98.8-156.6) respectively, P < 0.05). No significant correlations were found between insulin sensitivity and PTH (rs = -0.21), 1,25(OH)2D (rs = -0.14), ionized calcium (rs = -0.11) and inorganic phosphate (rs = 0.34). Beta-cell function did not correlate with PTH (rs = 0.15), 1,25(OH)2D (rs = 0.04), ionized calcium (rs = 0.23) or inorganic phosphate (rs = -0.35). CONCLUSION: Insulin insensitivity is present in PHPT even in the absence of hypertension and obesity, and may be the cause of glucose intolerance and diabetes. PHPT subjects with reduced beta-cell function are more likely to develop glucose intolerance.

Adult↗
PubMed1994

Tuberculous radiculomyelitis (arachnoiditis): myelographic (and CT myelographic) appearances.

Tuberculous radiculomyelitis (arachnoiditis) remains one of the important causes of paraplegia in India. The diagnosis usually rests on clinical history and examination, and on laboratory findings in the cerebro-spinal fluid (CSF). Few descriptive reports are available of the myelographic appearance, with water-soluble contrast media, in tuberculous radioculomyelitis (arachnoiditis). A retrospective review of 21 myelograms and 10 computed tomographic (CT) myelograms, in 14 patients with tuberculous radiculomyelitis, was carried out, with a view to describing, in detail, the radiographic features. An attempt was made to assess the use of the radiologic procedures in diagnosis and follow up in these patients. Conventional myelographic findings included block (8/14), irregular subarachnoid space (9/14), filling defects (8/14), sluggish contrast flow (2/14), root thickening (3/14) and atrophic cord (2/14). Computed tomographic myelography showed reduced contrast density in portions of the opacified CSF ring around the cord in affected region (6/7) and, in addition, demonstrated septa and adhesions. Intravenous contrast CT was not found to be useful (2/2). Follow-up studies showed partial resolution (3/6), deterioration (1/6) and status quo of radiological findings (2/6). Although these changes can be seen in chronic radiculomyelitis (arachnoiditis) from other causes, such as leukaemic infiltration/lymphoma, other chronic central nervous system infections and iatrogenic causes, including repeated intrathecal injections, conventional myelography appeared to be useful for diagnosis and follow up in tuberculous radiculomyelitis (arachnoiditis).

Adult↗
PubMed1994

Extra gonadal germ cell tumours: report of two cases.

Extra gonadal germ cell tumours (EGGCT) in women are rare. We report here two such patients. The clinical and laboratory features were--young age, 25 and 22 years, midline location (mediastinum, scalp), elevated tumour marker and normal ovaries on CAT scan. The histological subtype was embryonal carcinoma in both cases. Complete response (CR) was achieved with cisplatin based chemotherapy (CT). Both patients had return of normal ovarian functions and have delivered normal babies (1st patient one, 2nd patient 2 babies). Both remain asymptomatic and disease-free at 30 + and 55 + months follow-up. We conclude that patients with EGGCT after treatment with cisplatin based CT achieve CR with return of normal ovarian functions and prolonged survival.

Adult↗
PubMed1994

Increased mortality due to cardiovascular disease in type 1 diabetic patients transplanted for end-stage renal failure.

The graft and patient survivals following renal transplantation in all Type 1 diabetic patients transplanted within the North-West of England between 1981 and 1990 at Manchester Royal Infirmary were studied. Fifty-two Type 1 (insulin-dependent) diabetic patients with end-stage renal failure due to diabetic nephropathy were transplanted during this period. They were compared to controls matched for age, sex, and year of transplantation and also to all 904 patients transplanted during the same period. Graft survival rates at 1 and 5 years in the diabetic patients were lower (80.8% and 62.1%, respectively), compared to controls (88.9% and 77.9%, respectively, p = 0.02) but were similar to those seen in all grafts (80.4% and 59.0%, respectively, p = NS). Actuarial patient survival rate at 5 years was lower in diabetic patients (76.3%) compared to the control group (94.2%, p = 0.003). Myocardial infarction was the main cause (60%) of death in diabetic patients. The results of this large recent series indicate that good graft and patient survival rates can be obtained in Type 1 diabetic patients, although they remain poorer than those of patients with non-diabetic renal disease. More rigorous pretransplantation cardiac assessment and treatment before acceptance of Type 1 diabetic patients for renal transplantation may help to improve patient survival.

Adult↗
PubMed1994

The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population-based study.

The prevalence of peripheral neuropathy, peripheral vascular disease, and foot ulceration in Type 2 diabetic patients in the community were determined in a community-based study. Eight hundred and eleven subjects (404 male, 407 female, mean age 65.4 (range 34-90) years, diabetes duration 7.4 (0-50) years) from 37 general practices in three UK cities were studied. Neuropathy was diagnosed clinically using modified neuropathy disability scores which were ascertained using structured interviews and clinical examinations by one observer in each city. Peripheral vascular disease was diagnosed if a history of revascularization was present or > or = 2 foot pulses were absent. History of current or previous foot ulceration was recorded. The prevalence of neuropathy was 41.6% (95% confidence limits 38.3-44.9%) and the prevalence of PVD, 11% (9.1-13.7%). Forty-eight percent of neuropathic patients reported significant neuropathic symptoms. Forty-three patients (5.3% (3.8-6.8%)) had current or past foot ulcers; 20 of these were pure neuropathic ulcers, 13 neuroischaemic, 5 pure vascular, and 5 were unclassified. Multiple logistic regression showed history of amputation, neuropathy disability score, and peripheral vascular disease to be significantly associated with foot ulceration after adjusting for age and diabetes duration. A substantial proportion of Type 2 diabetic patients, often elderly patients who do not attend hospitals, suffered from peripheral neuropathy and peripheral vascular disease. These patients are at risk of foot ulceration and may benefit from preventive footcare.

Adult↗
PubMed1994

Alkali-labile photolesions mapping to purine sites in ultraviolet-irradiated DNA.

Gel sequencing experiments with the 5'- and 3'-end-labeled oligonucleotides d(A3GA4GA5GA6GA3G) and d(AT)10 have demonstrated that dimeric adenine photoproducts and thymine-adenine photoadducts constitute alkali-labile lesions in UV-irradiated DNA. On treatment with hot piperidine, DNA strand breakage occurs predominantly at the sites of 5'-adenines in the dimeric photoproducts and of 3'-adenines in the thymine-adenine photoadducts. With 5'-end-labeled oligonucleotides of mixed sequence, major UV-induced loci for alkaline cleavage map to purine bases flanked on their 5'-side by two pyrimidines. This behavior does not arise from enhanced photoreactivity of purines in this sequence context as has been inferred from photofootprinting studies. Instead, as shown by 3'-labeling and selective substitution with 5-methylcytosine, it results from the anomalous electrophoretic mobility of 5'-end-labeled fragments produced by alkaline cleavage of DNA at adjacent pyrimidine (6-4) pyrimidone photoproducts.

Alkalies↗
PubMed1994

Antigenic diversity in the circumsporozoite protein of Plasmodium falciparum abrogates cytotoxic-T-cell recognition.

Genetic analysis of field isolates of Plasmodium falciparum has shown selective accumulation of point mutations within the immunologically sensitive sites of the circumsporozoite (CS) protein, a vaccine candidate against malaria. This raised concern whether a vaccine containing the sequence of a selected strain of P. falciparum would be able to confer protection against other variant parasites. The answer to this question remained speculative, and in this study, we have formally tested the immunological impact of such natural variations within a known cytotoxic-T-cell (CTL) epitope, which is recognized by both human and murine CTLs. With a murine model, CTLs were generated against the 7G8 strain of P. falciparum. The ability of these CTLs to lyse histocompatible targets that were pulsed with synthetic peptides corresponding to polymorphic sequences of Brazilian, Papua New Guinean, and The Gambian isolates was determined. While these CTLs were able to recognize three of the four variant CS sequences found in Brazil and Papua New Guinea, they failed to recognize four of the five variant CS sequences found in The Gambia. Among the peptides that lost their reactivity to 7G8-specific CTL, all except one had amino acid variation in more than one residue. On the other hand, only one of the four peptides that showed a positive reaction had amino acid substitutions in more than a single residue. Thus, our findings demonstrate that natural amino acid variations in the CS protein abrogate CTL recognition. Therefore, it is important to consider the implications of these results in designing CS protein-based vaccines.

Amino Acid Sequence↗
PubMed1994

Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D.

Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes. The test was repeated 0.5, 1, 3 and 5 months after starting treatment. Serum calcium increased glucose intolerance from 1.76 to 2.0, 2.08, 1.96 and 2.0 mmol/l, respectively; vitamin D reached supraphysiological levels initially and returned to normal levels, and parathyroid hormone levels were normalized. Her weight did not change during treatment. Glucose tolerance improved during treatment and achieved glucose was 9.4, 8.6, 9.2 and 9.0 mmol/l at 0.5, 1, 3 and 5 months, respectively; insulin sensitivity did not change. Beta-cell function improved from 101% at diagnosis to 126%, 147%, 173% and 198% at 0.5, 1, 3 and 5 months, respectively. Improvement in beta-cell function and consequently in glucose tolerance is likely to have been due to correction of hypocalcaemia, vitamin D deficiency and secondary hyperparathyroidism.

Aged↗
PubMed1994

Clinical predictors of Japanese encephalitis.

Over a 5-year period, virological investigations for Japanese encephalitis (JE) were conducted in children presenting with acute encephalopathic illness. Clinical features of JE-positive patients (n = 116) were compared with patients in whom the diagnosis could be excluded (n = 57). Multivariate analysis by logistic regression revealed that two clinical signs--central hyperpneic breathing pattern and extrapyramidal signs--were significant predictors of the diagnosis. Application of the model yielded a sensitivity of 41.3% and a specificity of 80.7% with positive and negative predictive values of 81.3 and 40.3%, respectively. This indicates that the model may be helpful in making the diagnosis but not in excluding it. The model should be further validated in different areas where the disease is prevalent.

Child↗
PubMed1994

Role of angiogenesis in patients with cerebral ischemic stroke.

BACKGROUND AND PURPOSE: Stroke is one of the most common causes of mortality and morbidity in the Western world. It results from the occlusion of a cerebral artery followed by severe disturbances in blood supply through microvessels to brain tissue. Despite an extensive literature its pathophysiology is poorly understood, and this has severely impeded the logical development of therapy. METHODS: Brains were obtained from 10 patients aged 46 to 85 years with survival times of 5 to 92 days after their stroke. Infarcted areas and representative control tissues from the contralateral uninvolved brain hemisphere were collected. Microvessel density was measured microscopically. A total of 6520 microvessels were scored in 10,801 areas. The level of activation of the endothelial cells was studied by immunohistochemistry using three monoclonal antibodies, viz, E-9, raised against activated endothelial cells; IG11, recognizing vascular cell adhesion molecule-1; and anti-proliferating cell nuclear antigen. Angiogenic activity in tissue extracts was examined using an in vivo chicken chorioallantoic membrane assay. RESULTS: There was a statistically significant increase in the number of microvessels (Wilcoxon log-rank test; P < or = .01) in 9 of 10 infarcted brain tissues when compared with their contralateral normal hemisphere. In these patients the higher blood vessel counts correlated with longer survival, as ascertained by Spearman's p analysis (P < .02). The number of microvessels filled with blood cells was significantly lower in the infarcted hemispheres (P < .01). In contrast, statistically significant increased numbers of empty microvessels occurred in infarcted tissues compared with the contralateral hemisphere. Monoclonal antibody E-9 reacted weakly with normal-brain vascular endothelial cells; anti-proliferating cell nuclear antigen and IG11 were virtually negative. All three antibodies strongly stained the blood vessels of stroke tissues. The stroke tissues contained angiogenic activity, as shown by the induction of new blood vessels in a chorioallantoic membrane assay. CONCLUSIONS: We have shown that stroke causes active angiogenesis that is more developed in the penumbra. Further experiments are needed to determine if this angiogenesis has beneficial effect.

Aged↗
PubMed1994

A conceptual model of overexertion [correction of oxerexertion], safety, and risk of injury in occupational settings.

A conceptual generic model for fatigue-mediated overexertion, margin of safety, and job-related risk of injury is proposed. The model has been built with the variables of force, effective exposure in time domain, and motion of the exertion in space. With the proposed model, the physical risk factors can be identified and quantified. It also allows one to gauge a relative contribution of various integral factors involved in fatigue-mediated occupational injuries. Although the model is based on established relationships between the job variables (strength [force], frequency-duration of exposure, recovery from exposure, and range of required motion) and the injuries sustained, it has not been validated within any single study. The model provides a framework for numerous validation studies. With availability of more information through such studies, the model can be appropriately refined for accuracy of its prediction.

Accidents, Occupational↗